Streptococcus is a genus of spherical shaped Gram-positive bacteria. Clinically, individual species of Streptococcus are classified primarily based on their Lancefield serotyping—according to specific carbohydrates in the bacterial cell wall. These are named Lancefield groups A to T. However the pathogens in these different groups share many similarities at the genetic level. For example Streptococcus equi (which is in group C, and which is the causative agent of equine strangles) shares 80% genome identity with the human pathogen S. pyogenes (which is in group A, and which is the causative agent of many human conditions including strep throat, acute rheumatic fever, scarlet fever, acute glomerulonephritis and necrotizing fasciitis). Additionally the two organisms share many near identical toxins and virulence factors.
Streptococci are further characterised via their haemolytic properties. Alpha haemolysis is caused by a reduction of iron in haemoglobin giving it a greenish color on blood agar. Beta only haemolysis is complete rupture of red blood cells giving distinct, wide, clear areas around bacterial colonies on blood agar. Other streptococci are labeled as gamma haemolytic.
Strangles is a disease characterised by nasal discharge and fever, followed by abscessation of local lymph nodes. The swelling of the lymph nodes in the head and neck may, in severe cases, restrict the airway and it is this clinical feature that gave the disease ‘strangles’ its name. Morbidity rates of up to 100% are reported and mortality as a result of disseminated abscessation (‘bastard strangles’) may occur in 10% of cases (Timoney, 1993a). Strangles is one of the most frequently diagnosed equine diseases worldwide. Recent outbreaks in Thoroughbreds have further highlighted the need for the development of improved therapies. Antibiotic treatment is usually ineffective despite S. equi's susceptibility to most antibiotics in vitro. Clinical signs following treatment have been reported to abate only until treatment is withdrawn. This relapse is probably due to the lack of sufficient vascularity in the abscess to enable antibiotic penetration to therapeutic levels and illustrates the importance of the development of an effective preventative vaccine (Harrington et al., 2002). Approximately 10% of horses that recover from strangles become carriers of the disease, harbouring the infectious agent in chondroids located in the guttural pouch. These carriers are capable of infecting other naïve horses and continue the spread of disease (Chanter et al., 2000, Newton et al., 1997, Newton et al., 2000). Therefore, a major goal of vaccine design is not only to protect against strangles, but also to prevent development of the carrier state.
Progress in the development of an effective strangles vaccine has been slow. Vaccines against the disease have been known for a long time (Bazeley, 1940 and Bazeley, 1942), but have either proved ineffective or suffer from undesirable side effects.
Four kinds of vaccines are available: a) vaccines based on classical bacterins, b) sub-unit vaccines based on the M-protein, an immunogenic protein, c) Chemically attenuated live Streptococcus equi and d) Genetically attenuated live Streptococcus equi. 
Conventional vaccines containing inactivated whole bacteria or extracts have shown little efficacy and often induce adverse reactions (Jorm, 1990, Timoney and Eggers, 1985). Classical vaccines based on bacterins or subunits are e.g. available through Fort Dodge Laboratories and Coopers Animal Health.
Those vaccines that specifically target the M-protein of S. equi, showed promise in mouse vaccination challenge studies (Meehan et al., 1998), but failed to demonstrate significant protection in horses despite the generation of M-protein reactive antibodies (Timoney et al., 1997, Sheoran et al., 2002).
Similarly, a recombinant S. equi hyaluronate associated protein (HAP) vaccine, was partially protective in mice (Chanter et al., 1999), but failed to prevent the development of strangles in vaccinated horses (N. Chanter unpublished results).
The basis and duration of protective immunity following natural infection is not fully understood, but in the majority of animals that recover from strangles immunity is believed to last for >5 years (Hamlen et al., 1994; Sweeney et al., 2005; Todd 1910; Woolcock, 1975).
A non-specifically attenuated vaccine strain for intranasal inoculation, the ‘Pinnacle I.N.’ strangles vaccine, is marketed by Fort Dodge (Timoney, 1993b). This acapsular strain was derived following chemical mutagenesis to induce random mutations throughout the bacterial genome (Timoney, 1993b). Such non-defined point mutations are prone to back mutation and thus to reversion to full virulence and although this vaccine may protect up to 100% of horses (Timoney, 1993b, Walker and Timoney 2002), it has not been licensed for sale in Europe due to safety concerns. These include nasal discharge, lymphadenectasis and a 5% risk of submandibular abscesses following IN vaccination (Timoney, 1993b). US2006110411 (WYETH FORT DODGE LAB (US)) relates to compositions comprising live, attenuated S. equi. 
Recently, an Intervet live attenuated vaccine strain TW 928 has been approved for sale in Europe, marketed as ‘Equilis StrepE’. This strain was attenuated by the partial deletion of the aroA gene and was 104-fold attenuated during intraperitoneal mouse challenge studies (Hartford et al., 1999). The TW 928 vaccine strain was attenuated in six horses with no signs of disease apparent at post mortem examination four weeks after intranasal challenge (Hartford et al., 1999). Intramuscular vaccination of horses with strain TW 928 conferred 100% protection from subsequent S. equi challenge. However, severe injection site reactions precluded the use of this route for future studies. Further, contamination of needles to be used for the administration of other products with the Equilis StrepE vaccine have also led to abscess formation at the intramuscular injection site (Kemp-Symonds et al., 2007).
In order to minimise injection site reactions and retain some protective efficacy, sub-mucosal vaccination with 109 cfu of the TW 928 strain into the inside of the upper lip was evaluated. Using this method, small pustules formed over a period of one week from which the TW 928 strain could be isolated. Horses were 50% protected from intranasal S. equi challenge and a further 25% of vaccinates had reduced clinical signs of disease. The presence of these pustules may be critical for the generation of an efficacious immune response since on dose reduction reduced injection site reactions correlated with decreased protection (Jacobs et al., 2000).
We have also observed cases of sub-mandibular lymph node abscessation in horses recently vaccinated with Equilis StrepE. In three of these cases we have confirmed by genetic analysis that the causal agent was the vaccine strain (Kemp-Symonds et al., 2007; Waller et al., unpublished data).
In addition, an undetermined proportion of the 25% of vaccinated horses, which on exposure to virulent S. equi suffer reduced clinical signs may go on to become carriers of virulent field strains of S. equi without being diagnosed. Such a scenario is of major concern to disease prevention strategies.
Finally, the vaccine suffers from only a 3-month duration of immunity, although boosting of horses vaccinated up to six months previously in the face of an outbreak has been shown to improve clinical outcome and extends the usefulness of this vaccine.
Overall, ‘Equilis StrepE’ is a promising advance over the Pinnacle strain (most notably in its lower risk of reversion). However, it is only recommended for use in horses of high or moderate risk of strangles where acquisition of a short duration of immunity is advantageous. Additionally, it suffers a number of drawbacks as discussed above.
It will be appreciated that novel vaccine strains which could overcome one or preferably more than one of these drawbacks would provide a contribution to the art.